EFFICACY OF ANTHELMINTICS AGAINST CATTLE NEMATODES

The efficacies of fenbendazole and thiabendazole against artifically acquired cattle nematodes and the efficacies of fenbendazole, prabendazole and levamisole against naturally acquired cattle nematodes were studied in western Victoria. Fenbendazole significantly (P less than 0.05) reduced numbers of late and early fourth stage larvae (greater than 96%), artificially acquired Cooperla spp (100%) and naturally acquired adult Ostertagia ostertagi (98%) and Trichostrongylus axei (90%). Thiabendazole significantly reduced numbers of artificially acquired late fourth stage larvae (83%) and parbendazole significantly reduced numbers of adult O. ostertagi (72%) in one group of cattle. Fenbendazole was the most effective anthelmintic.     

The efficiency of levamisole, thiabendazole and fenbendazole against naturally acquired infections of Ostertagia ostertagi in cattle

In two experiments, conducted in cattle with naturally acquired infections of Ostertagia ostertagi, comparative assessments were made of the anthelmintic efficiency of levamisole, thiabendazole and fenbendazole, each at 1.0, 1.5 and 2.0 times the recommended dose rate. Variable efficiencies of 81 and 49 per cent for levamisole, 86 and 56 per cent for thiabendazole were obtained against adult O ostertagi. Neither drug showed substantial activity against early fourth stage larvae. Efficiency of fenbendazole against adult O ostertagi was consistently high; 85 and 89 per cent in the two experiments respectively. In the first experiment in which cattle were slaughtered two to three days after treatment, only 22 per cent of inhibited early fourth stage larvae were removed whereas in the second experiment when slaughter took place 10--11 days after treatment, this efficiency was 89 per cent. There was no increased effect of increased dose rates on treatments with thiabendazole or fenbendazole. The activity of levamisole against adult worms and inhibited larvae was increased at twice the recommended dose rate.     

Efficacy of albendazole, levamisole and fenbendazole against gastrointestinal nematodes of cattle, with emphasis on inhibited early fourth stage Ostertagia ostertagi larvae.

An experiment was conducted to compare the anthelmintic efficacy of albendazole (ABZ), levamisole (LEV) and fenbendazole (FBZ) against inhibited early fourth stage larvae (EL4) of Ostertagia ostertagi during April in Louisiana. Forty cross-bred beef heifers (average weight 165 kg) were acquired during winter and grazed on pastures contaminated with O. ostertagi and other nematodes until early April. The cattle were weighed and randomly allotted into four groups of ten animals on 6 April and treatments were administered on 7 April. Experimental groupings were: Group 1, non-treated controls; Group 2, ABZ by oral drench at 10 mg kg-1; Group 3, LEV by topical, pour-on administration to back midline at 10 mg kg-1; Group 4, FBZ by oral drench at 10 mg kg-1. Equal numbers of cattle from each group were slaughtered daily between 10 and 13 days after treatment. Mean numbers of O. ostertagi developmental stages present in untreated controls were: adults, 13,714; developing L4 (DL4), 6487; inhibited EL4, 21,719. The mean percentage of inhibited EL4 was 51.8. Smaller numbers of Haemonchus placei, Trichostrongylus axei and Cooperia spp. were recovered uniformly in control cattle. Percentage reduction values for the three compounds against O. ostertagi adults, DL4 and EL4, respectively, were: ABZ, 99.0, 95.3, 84.9; LEV, 1.0, 21.8, 32.1; FBZ, 99.2, 97.2, 97.5. Differences between ABZ and LEV EL4 counts were not significant, but in all other cases worm counts in ABZ and FBZ-treated cattle were significantly lower (P less than or equal to 0.05) than in LEV-treated and control cattle. Both ABZ and FBZ were 98-100% effective against Haemonchus adults and L4, T. axei adults, and Cooperia spp. adults and L4. LEV was 100% effective against Haemonchus adults and L4, 85.6% against T. axei, and 94.6% and 89.59% effective against Cooperia spp. adults and L4, respectively.     

Efficacy of fenbendazole against inhibited larvae of Ostertagia ostertagi in yearling cattle

Efficacy of fenbendazole, at doses of 7.5 and 10.0 mg/kg of body weight, against inhibited early 4th-stage larvae of Ostertagia ostertagi and other nematodes of the abomasum and intestinal tract, was investigated in naturally infected yearling heifers in late May 1982. In Louisiana, this is near the end of the period (March to May) in which maximal numbers of inhibition-prone larvae are acquired. The mean numbers of O ostertagi in 10 untreated control cattle were: adults, 4,880; developing 4th-stage larvae, 12,546; and inhibited early 4th-stage larvae, 167,931. At the 7.5 mg/kg dose level (10% liquid suspension) in 10 cattle, percentage reduction of O ostertagi in comparison with controls was: adults, 95.7%; developing 4th stages, 91.1%; and inhibited 4th stage, 55.0%. Percentage reductions of other genera were as follows: abomasum--Trichostrongylus axei, 99.6%; Haemonchus sp, 95.1%; intestinal tract--Cooperia spp, 97.8%; Trichostrongylus colubriformis, 100.0%; and Oesophagostomum radiatum 4th stage and adults, 100.0%. At the 10.0 mg/kg dose (10% liquid suspension) in 11 cattle, the percentage reduction of O ostertagi in comparison with controls was: adults, 98.6%; developing 4th stages, 92.9%; and inhibited 4th stage, 80.0%. Percentage reductions of other genera were: abomasum--T axei, 99.9%; Haemonchus sp, 98.8%; intestinal tract--Cooperia spp, 99.3%; T colubriformis, 100.0%; and Oes radiatum 4th stage and adults, 100.0%. Variability of efficacy against inhibited larvae was observed, particularly at the 7.5 mg/kg dose; at this dose, 7 of the 10 heifers in the group yielded in excess of 54,000 surviving larvae.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activity against Ostertagia ostertagi of low doses of oxfendazole continuously released from intraruminal capsules in cattle.

Slow release from intraruminal capsules of 0.48 mg/kg oxfendazole per day for 5.5 days gave percentage efficiencies of 99 +/- 0.6, 86.6 +/- 6.3 and 93.1 +/- 4.5 for the removal of adult worms, developing 4th stages and inhibited larvae of Ostertagia ostertagi respectively. These efficiencies were not significantly different from those obtained from a single oral dose of 2.5 mg/kg. Peak plasma levels of oxfendazole were similar for the 2 types of administration but high levels were maintained longer in cattle given capsules.     

Evaluation of oxfendazole against natural infections of gastro-intestinal nematodes and lung-worms in calves.

The anthelmintic activity of oxfendazole (Syntex) was tested in calves at dosages of 2-5 and 5-0 mg per kg. At both dose levels, oxfendazole showed 100 per cent efficacy against adult Ostertagia ostertagi, O lyrata, O cremensis, fifth stage Ostertagia spp and adult Haemonchus spp. Against adult Cooperia oncophora, efficacy was 99.8 per cent and 100 per cent at doses of 2.5 mg per kg and 5.0 mg per kg respectively while at both dose levels 100 per cent activity was recorded against C surnabada and fourth and fifth stage Cooperia spp. One hundred per cent efficacy was obtained with both dose levels against adult and fifth stage Dictyodaulus viviaprus; against Trichuris spp, percentage efficacy was 92 and 100 per cent at doses 2.5 and 5.0 mg per kg respectively. Oxfendazole showed higher efficacy than levamisole against Ostertagia spp but against the other species encountered, both anthelmintics possessed similar efficacy. Both anthelmintics significantly increased the calves' weight gains.     

Persistence of dead Ostertagia ostertagi in the abomasal mucosa following anthelmintic treatment

Anthelmintic trails, conducted with albendazole, fenbendazole and ivermectin for efficacy against gastrointestinal nematodes, principally inhibited early fourth larval stages of Ostertagia ostertagi in naturally infected cattle. Cattle wee slaughtered seven to 20 days after treatment. O ostertagi was the predominant abomasal nematode recovered with occasional small numbers of Haemonchus species and Trichostrongylus axei. Control calves uniformly had very large O ostertagi infections, primarily early fourth stage larvae. Viable surviving worms and variable numbers of dead and degenerate worms were recovered in abomasal contents and washings. These O ostertagi larvae and adults were characterised by adherent debris or proteinaceous material, degenerated cuticles and distortion of internal structures. This study demonstrated the necessity for proper timing of slaughter for anthelmintic trial evaluation to allow clearance of dead nematodes, specifically O ostertagi larvae which are sequestered in the abomasal glandular tissue. Nematode collection within seven to 12 days after treatment will include dead and degenerate larval nematodes. The peripheral coating of larvae was suggestive of the Splendore-Hoeppli effect which has been associated with immunological responsiveness. The antigenic stimulus for this material and the lymphocyte and eosinophil infiltration was suspected to be early fourth stage O ostertagi larvae within the mucosa but was not identified definitively.     

THE ANTHELMINTIC EFFICIENCY OF LAEVO-TETRAMISOLE HYDROCHLORIDE AGAINST NEMATODE PARASITES OF SHEEP AND CATTLE

Critical anthelmintic tests and controlled trials were used to assess the efficiency of laevo -tetramisole hydrochloride against nematode infections in sheep and cattle.
In sheep, oral dose rates of 5 mg/kg and above were 94 to 100% effective against adult Haemonchus contortus , intestinal Trichostrongylus spp, Nematodirus spp, Oesophagostomum columbianum, O. venulosum and Chabertia ovina . A dose rate of 7.5 mg/kg was required for consistently high activity against Ostertagia spp, but activity against Trichostrongylus axei remained variable at this dose level. Efficiency against Trichuris ovis ranged from 76 to 100% at a dose rate of 10 mg/kg. The drug was 94 to 100% effective against 7-day old and 14-day old H. contortus , intestinal Trichostrongylus spp and O. colun bianum infections, and 83 to 89% effective against 14-day old Ostertagia spp and T. axei , at a dose rate of 5 mg/kg. Seven-day old Ostertagia spp larvae were highly resistant at a dose rate of 10 mg/kg, while activity against T. axei infections of the same age appeared variable at 5 and 10 mg/kg.
In cattle, subcutaneous treatment at dose rates of 1.5 mg/kg and above, and oral treatment at 7.5 mg/kg, were 93 to 100% effective against adult Haemonchus placei , intestinal Trichostrongylus spp, Nematodirus helvetianus, Cooperia spp and Oesophagostomum radiatum , and 84 to 98% effective against Ostertagia ostertagi . Against Trichostrongylus axei , a rate of 5 mg/kg subcutaneously was 83% effective, and a rate of 7.5 mg/kg orally 97% effective, while these dose rates gave 88 to 100% clearance of adult Dictyocaulus viviparous .     

Efficacy of doramectin against naturally acquired adult and inhibited larval infections by some nematode parasites in cattle in New Zealand

A study was conducted to determine the therapeutic efficacy of 1% doramectin injected subcutaneously at 200 microg/kg into cattle harbouring naturally acquired infections of inhibited Ostertagia ostertagi larvae. Sixteen yearling Friesian bulls, grazed without anthelmintic treatment throughout the autumn-winter, were selected on the basis of similar body weights and serum pepsinogen activities. After removal from pasture on day -23 they were weighed and randomly assigned to two treatment groups on the basis of this weight. On day 0, one group was given saline (1 ml/50 kg) while the second was treated with doramectin (200 microg/kg). Both treatments were given by subcutaneous injection. All stock were slaughtered 14-15 days after treatment. Moderate to high levels of adult O. ostertagi and Trichostrongylus axei and early and late 4th larval stages of O. ostertagi were recovered from saline-treated calves at necropsy. Doramectin was highly effective in eliminating all stages of O. ostertagi (99.9%; p<0.0001) and T. axei (100%; p<0.0001). No evidence of lesions were detected at the injection sites at necropsy. These results confirm that doramectin is an extremely effective broad-spectrum avermectin anthelmintic with efficacy against inhibited as well as maturing larval and adult forms of O. ostertagi.     

Drug resistance in ostertagiasis

Benzimidazole- and levamisole-resistant Ostertagia circumcincta from sheep have been reported from several countries, but there are no reports of anthelmintic-resistant O. ostertagi in cattle, where resistance has been confirmed in controlled trials. The reasons for this may include (1) the biology of the worm, (2) avoidance of drug action by inhibition, (3) host metabolism of drugs, (4) less anthelmintic used in cattle than in sheep, (5) high costs of controlled trials, (6) lack of adequate in vitro tests to detect resistant worms and (7) lack of reporting of anthelmintic failures. Reduced efficacy of the anthelmintics levamisole and thiabendazole to adult O. ostertagi and of modern benzimidazoles to the inhibited L4 larvae has been reported in cattle. This latter effect might, in part, represent a stage-specific expression of resistance. Although anthelmintic resistance in O. ostertagi is not known to be a problem at present, it could potentially become a serious issue.     

Controlled trials of the anthelmintic oxfendazole in ewes and lambs naturally infected with gastrointestinal nematodes.

Oxfendazole doses at a rate of 5 mg per kg, before or after lambing, reduced nematode egg output to insignificant levels in ewes, most of which were not exposed to re-infection. Ewes treated with oxfendazole had a significantly lower egg output than those treated with levamisole, although the latter anthelmintic was also highly effective. In lambs, oxfendazole at a dose rate of 5 mg per kg, showed 100 per cent efficacy for Ostertagia circumcincta, O trifurcata, Teledorsagia davtiani, Trichostrongylus axei, T vitrinus, T colubriformis, Nematodirus battus, N filicollis, immature Nematodirus, Chabertia ovina, and 93 per cent efficacy for Trichuris spp. Levamisole showed similar efficacies but did not remove Trichuris.     

Efficacy of oxfendazole against inhibited Ostertagia ostertagi in naturally infected cattle.

Oxfendazole was administered to pregnant cows at 2.5 and 5 mg/kg body weight to determine the anthelmintic efficacy against naturally acquired larvae which became inhibited at the early 4th stage. The experimental design included three groups of orally-treated cows, that is, 10 placebo treated control cows, 11 cows treated with 2.5 mg/kg of oxfendazole and 10 cows treated with 5.0 mg/kg of oxfendazole. Oxfendazole at 2.5 mg/kg body weight was 82 and 94% effective against EL-4 and adult O. ostertagi, respectively. At 5 mg/kg, Oxfendazole was 95 and 99% effective against EL-4 And adult O. ostertagi, respectively. The results suggested the use of a field dosage level of 5 mg/kg body weight oxfendazole where inhibited larvae may be encountered.     

Anthelmintic efficacy of oxfendazole in calves

Oxfendazole, methyl [5-(Phenylsulfinyl)-1H-benzimidazol-2-yl]carbamate given to calves at dose level of 2.5 mg/kg as a paste, as a bolus, or as a drench resulted in excellent (97 to 100%) anthelmintic efficacy against mature Ostertagia ostertagi, Trichostrongylus axei, Cooperia oncophora, C mcmasteri, C pectinata, C punctata, Nematodirus helvetianus, Trichostrongylus longispicularis, Chabertia ovina, and Oesophagostomum radiatum. Against the early 4th stage larvage of O ostertagia and N helvetianus, these formulations had anthelmintic efficacies of 71% to 87% and 21% to 65%, respectively. As the result of differences in drug intake by individual calves, a pelleted feed additive given as top dress on chopped alfalfa hay gave an unsatisfactory mean anthelmintic response. Anthelmintic action in individual calves ranged from none to 98--100%.     

Metabolite concentrations in plasma following treatment of cattle with five anthelmintics

Plasma concentrations of anthelmintics and their metabolites were determined after cattle were treated at recommended dose rates and routes of administration. Fenbendazole, oxfendazole, febantel, albendazole and thiabendazole were given orally and oxfendazole was also administered with an intraruminal injector. After fenbendazole, oxfendazole and febantel were administered, fenbendazole, oxfendazole and fenbendazole sulphone were all detected in plasma in each case. However, there were marked differences between the three anthelmintics in the peak concentrations and areas under the plasma concentration/time curve (AUC) of these three metabolites. Intraruminal administration of oxfendazole produced higher AUC for fenbendazole and fenbendazole sulphone than did oral administration. Albendazole sulphoxide and sulphone were detected in cattle plasma after albendazole administration but no parent drug was present. These metabolites disappeared more rapidly in cattle than has been reported for sheep. Only 5(6)hydroxythiabendazole was detected in cattle plasma after thiabendazole treatment.     

Efficacy of oxfendazole against inhibited larvae of Ostertagia ostertagi in naturally infected calves in the southern USA

Forty yearling calves were assigned to four equal groups; three of the groups were treated with oxfendazole at dose rates of 6.75 mg/kg, 4.50 mg/kg, or 2.25 mg/kg bodyweight while the fourth group served as an untreated control. The calves were native to north-east Mississippi, USA, and harboured natural infections of gastrointestinal nematodes. The study was conducted during July when inhibited early fourth-stage larvae may be found in large numbers after their acquisition in the spring. The calves were maintained in separate groups on concrete-floored pens for 17 days before the intraruminal administration of oxfendazole. Seven days after treatment, the calves were slaughtered and the gastrointestinal parasites counted. At all the dose rates examined oxfendazole exhibited an efficacy of at least 99.4 per cent against adults of Haemonchus placei, Trichostrongylus axei, Bunostomum phlebotomum, Cooperia species, T colubriformis, Oesophagostomum radiatum, and Trichuris ovis. The efficacy against adult Ostertagia ostertagi was at least 99.4 per cent at dose rates of 6.75 and 4.50 mg/kg bodyweight, but decreased to 93.7 per cent at 2.25 mg/kg. The efficacy of oxfendazole against inhibited larvae of O ostertagi decreased with dose rate from 78.8 per cent at 6.75 mg/kg, to 58.9 per cent at 4.50 mg/kg and 20.3 per cent at 2.25 mg/kg bodyweight.     

EFFECTIVENESS OF ANTHELMINTIC TREATMENTS AGAINST LEVAMISOLE-RESISTANT OSTERTAGIA

Adult worms from a population of Ostertagia consisting of 88% O. circumcincta and 12% O. trifurcata were found to survive a double drench (14 mg/kg) of levamisole. An anthelmintic assay on this population found that against levamisole the LD50 was 11.95 mg/kg and the LD99 was 67.75 mg/kg. Three benzimidazoles were also tested against this population and the LD50 and LD99 were respectively thiabendazole 11.8 and 144.9 mg/kg, oxfendazole 0.17 and 6.10 mg/kg and albendazole 0.08 and 2.55 mg/kg. The percentage of worms killed by the recommended dose rate was levamisole 24%; thiabendazole 91%; oxfendazole 99% and albendazole 99%.     

MULTIPLE AND MULTIGENERIC ANTHELMINTIC RESISTANCE ON A SHEEP FARM IN KENYA

The anthelmintic efficacy of benzimidazoles (albendazole, fenbendazole and oxfendazole), levamisole, oral ivermectin and closantel was evaluated on a farm in Kenya using faecal egg count reduction test, larval cultures and a controlled slaughter trial. The results of this study indicated simultaneous resistance of Haemonchus contortus against benzimidazoles, levamisole and ivermectin, and of Trichostrongylus colubriformis and Oesophagostomum spp. against levamisole on the same farm. Ivermectin resistance developed to 47% within 15 months of first use. Closantel was effective against the benzimidazoles, levamisole and ivermectin resistant H. contortus.     

THE EFFECT OF DERMALLY APPLIED LEVAMISOLE AGAINST THE PARASITIC NEMATODES OF CATTLE

A series of trials to establish the anthelmintic efficiency of levamisole, when applied dermally to calves, is described. The levamisole base was formulated in a suitable solvent system at 100 g/l and applied dermally at a dose rate of 8 mg base/kg. This gave efficiencies of 97.1-100%, 88.5-100%, 100%, 98.7-100% and 89.2-100% against adult Haemonchus placei, Ostertagia spp, Cooperia spp, Oesophagostomum radiatum and Trichostrongylus axei, respectively. Activity against the immature stages of H. placei was recorded at 100%, and against immature Cooperia spp the range was 96.3-100%. Extremely variable results were obtained against immature Ostertagia spp, efficiency ranging from 0% to 100%. Efficiency against adult Dictyocaulus viviparus was in the range of 84-100%. The potential advantage of a dermally applied anthelmintic is discussed.     

Multiple anthelmintic resistance in Trichostrongylus colubriformis

Following the failure of anthelmintic treatment to control an outbreak of trichostrongylosis in sheep, multiple resistance to levamisole and oxfendazole was confirmed in field strains of Trichostrongylus colubriformis at the CSIRO Pastoral Research Laboratory, Armidale. Resistance in Trichostrongylus spp to levamisole was also confirmed on an adjoining farm. From the results of an experiment where lambs were treated at the recommended dose rate with one or both anthelmintics, it was estimated that 32% of T. colubriformis were resistant to levamisole, 19% to oxfendazole, and 12% to both drugs. Simultaneous administration of levamisole and oxfendazole resulted in an additive anthelmintic effect. Naphthalophos (36.6 to 51.2 mg/kg) was 93% efficient against the multiple resistant strain. The similar histories of anthelmintic usage at the CSIRO Pastoral Research Laboratory and on the northern tablelands of New South Wales generally, suggest that multiple anthelmintic resistance in T. colubriformis may soon emerge as a problem on the northern tablelands.     

Anthelmintics and control

Anthelmintic control of Ostertagia ostertagi in cattle presents some special problems because the arrested larval stage (hypobiotic EL4) tolerates all of the older anthelmintics. The only anthelmintics on the North American market that are effective against this stage as well as the adult and developing stages are ivermectin and fenbendazole. In addition to these, the newer broad-spectrum benzimidazoles and probenzimidazoles, albendazole, febantel, netobimin and oxfendazole, are effective and available in other countries. These anthelmintics can be used for prophylaxis of Type II ostertagiasis. The older anthelmintics, levamisole, morantel tartrate, thiabendazole, coumaphos, haloxon and phenothiazine, are effective against the adults and to some extent the developing stages of O. ostertagi so that they can be used to treat Type I ostertagiasis. They can also be used to prevent incoming larvae from establishing if they are administered continuously over a long period of time. This is possible with long term in-feed administration or by the use of the morantel slow release bolus. In cooler temperature regions, where cattle are housed over the winter, this bolus is given at turnout to remove any parasites in the animals and to kill incoming larvae for 60-90 days. This can prevent the build up of significant infective larvae on pasture so that very few arrested L4 larvae accumulate in the summer/autumn, effectively preventing Type II ostertagiasis from occurring later. The use of ivermectin and the newer benzimidazoles in intermittent or slow release devices should prove highly effective in the control of Type I and II ostertagiasis, as well as of subclinical ostertagiasis. To achieve maximum economic benefit, the use of anthelmintics should be based on sound epidemiological considerations, so that stock are not rapidly reinfected after treatment.